One Health: The interconnection of animal and human health
There’s a tendency to overlook the fact that human health and animal health are closely intertwined. As an Ethnozoology published paper put it, “we share hundreds of diseases with animals, and they are vectors for many diseases that afflict humans, but at the same time they are essential to many treatments and cures.”
While we none of us are ignorant any longer of the vector status of animal health’s impact on our own, the other angle of comparison is seemingly under-observed. To discuss just how connected the two are, pharmaphorum recently spoke with Dr Stefan Jahnecke, Veeva’s head of strategy for animal health, a veterinarian well-versed in the differences, especially when it comes to launching new products and navigating the regulatory landscape.
Zoonotic threats are not new
As is well-known these days, zoonotic influenza is a globally present disease caused by animal influenza viruses that cross the animal-human divide, infecting people. Examples include avian flu virus subtypes A(H5N1) and swine influenza virus subtypes A(H1N1). Yet, these animal viruses are distinct from human influenza viruses and do not easily transmit between humans, only sporadically spilling over – albeit, with high fatality rates.
As with Covid-19 vaccines, flu vaccines not only directly protect the recipient, but also prevent inter-species transmission, which can facilitate the emergence of new viruses. In the US, in addition to seasonal influenza vaccines for humans, there are 12 animal flu vaccines licensed, notably for swine. Pigs are vaccinated, while birds are not, and the lack of an oral vaccine for the mass vaccination of poultry presents a challenge for the poultry industry. In fact, we are in the midst of one of the largest avian flu outbreaks, which has resulted in the deaths of more than 58 million birds in the US alone, and influenza viruses like this one (H5N1) are an important area to watch for future pandemic risk.
“COVID really has, I think, renewed the sense of public awareness for zoonotic diseases in particular,” Dr Jahnecke commented. “The ones that are probably the best known are Ebola, rabies, avian influenza, and then Rift Valley fever and a few others. Those are the ones that come and go a little bit in the press. Zoonotic threats are not new. They have been here for a long time. In fact, there are different estimates, but around 70% of emerging diseases that infect humans come from animal populations or their products.”
Some reasons for this include human population growth, disruptions in land use, deforestation, and global warming; the latter, especially, drives mosquitoes – and malaria – further north.
“It's a very dynamic environment,” Dr Jahnecke said. “Then, also, international trade and the movement of humans contribute to that. Avian influenza has been in the press a lot of times. There is about a 50% fatality rate in humans that contract this type, mostly from contact with chickens [or] poultry. Most often, these are the labourers, the workers that deal with the animals. Just recently, in March, there was another strain that confirmed another human death in China, [reminding] us that it is an ongoing threat and those particular viruses are evolving steadily and very, very fast.”
Alongside preparing candidate vaccines for human seasonal influenza, the Centers for Disease Control (CDC) routinely develops candidates for new avian and swine influenza viruses that hold pandemic potential as part of their pandemic preparedness activities. However, flu vaccines protect against specific influenza viruses, with minimal cross-protection, so the challenge is first to identify the emerging animal influenza virus that is posing or may pose a risk to human health.
Vaccine development remains a challenge due to many factors and influenza vaccination in animals remains an important measure to control and prevent reassortment events and zoonotic transmission, as well as to reduce flu illness in humans and animals.
Additionally, West Nile virus is one of the top eight zoonotic diseases of national concern in the US, also serving as an example of the potential for collaborative vaccine development through coordination between human health and animal health. First detected in animals in the US in 1999, West Nile virus quickly spread to cause illness in humans, horses, and birds. Early on during the epidemic, veterinary and human vaccine candidates were developed in tandem and the data gathered from both programmes was shared across sectors to help inform the pathway to advanced clinical trials. Today, the West Nile virus vaccine is considered a core vaccine for horses.
One Health, One Medicine
This is why vaccination is crucial, and this is why the One Health effort matters.
In 2019, the American Society of Microbiology wrote of the concept of ‘One Health’ that it is defined as “the collaborative effort of multiple disciplines – working locally, nationally, and globally – to attain optimal health for people, animals, and the environment.” A broad concept, it encompasses topics ranging from antimicrobial resistance (AMR) to mental health, from biodiversity and climate to so much more.
“As far as mental health, I think in the One Health concept it has more to do with the fact that animals help reducing stress, anxiety,” Dr Jahnecke said. “There are numerous studies that point out that having a pet, for example, helps with mild to perhaps moderate mental health issues. When it comes to using mental health as a sort of research area, as you can imagine, there are a lot of challenges when it comes to psychiatric disorders or mental health disorders, translating them to animals. The key principle here that is talked about a lot, though, and more and more, is the human-animal bond.”
“More and more research goes into this,” he continued. “It's highly interesting and, at its foundation, very simple. We have evolved together with dogs for 30, 40, some say 50,000 years, and it's almost logical to assume that our genetic advancement was influenced by the presence of dogs and vice versa.”
And that includes scientific advancement, too.
“Many human disorders have been very well studied in clinical analogues, mostly in dogs,” Dr Jahnecke explained. “When we go and look at the translational area at the intersection between human health and animal health in the One Health concept, we're mostly talking about dogs, really. That, in a narrower sense, is also called One Medicine.”
But what are some of the diseases that are considered clinical analogues?
“Cancer, for sure,” Dr Jahnecke said. “Diabetes, hypertension, and congestive heart failure, to name a few, but also some of the chronic enteropathy like IBD and inflammatory bowel disease. Those are the diseases that occur spontaneously in dogs and increasingly become interesting also for us under this One Health or One Medicine concept.”
Antimicrobial resistance (AMR), however, is another, complicated matter.
“This is a big topic,” Dr Jahnecke stated. “It's being tackled on many fronts. There are approaches from regulatory bodies, the FDA or EMA, trying to reduce usage of antimicrobials and looking at ways to promote the judicious use of antibiotics in animal health. Some of the successes, the sales of veterinary antimicrobials, have dramatically declined over the last 10 years or so or more. In the EU, since 2011, they have declined by more than 40%. In the UK, by more than 50%, I believe. In the US, somewhat smaller, in the order of 30%, 35% to 38%.”
“We have a reduction that is happening, but there's also, from our customers, the animal health manufacturers, their efforts to help in this area,” he continued. “For example, the major animal health manufacturers have come together to create a roadmap to reduce the need for antibiotics and set targets by 2025. They pledged to deliver at least 100 new vaccines, at least 20 new diagnostic tools, and at least 20 new nutritional enhancement products. That comes along with a pledge to invest a certain amount of money in R&D, but also conduct risk analysis for every new antibiotic that is being brought to market, and some other examples.”
Animal health business units
Most of the animal-purposed drugs today stem from human pharmaceutical research historically.
“Since 2015, we had the first monoclonal antibody product in animal health, where you could say that some of the technology to develop those antibodies is coming from scientific advances in human health,” Dr Jahnecke explained. “I started my career in the animal health industry with Pfizer when Pfizer used to have an animal health business unit.”
However, fewer and fewer pharmaceutical companies still have an animal health business.
“Only about two large pharmaceutical companies still have an animal health business,” he said. “Those are the US Merck or MSD and Boehringer Ingelheim. All the other companies, whether it was Eli Lilly, or Pfizer, or Novartis, Bayer - they have either spun off or sold the business unit. This trend is still there, but with the emergence of new monoclonal antibody technologies, we see a similar shift to biopharmaceuticals in animal health to what we saw 10 years ago in human health.”
“The key opportunity, and maybe the big idea, is that in human pharma you have about 34%, 35%, 40% attrition in phase 2 because of the failure to demonstrate clinical efficacy,” Dr Jahnecke stated. “This is a huge problem. These high failure rates, combined with very few actual animal models that are predictive of success in human health, highlight the need for alternative approaches. That is the big idea, which is to leverage technology to de-risk a human health programme. Or to create an animal health product and thereby improve the net percent value of a new asset. That is, the opportunity to translate new technology, the opportunity for biotech start-ups.”
Animal health companies are facing an increasingly complex commercial environment, however, and have been forced to make do with either generic or niche systems not designed for their requirements.
“I would still say there's a lot of education necessary,” Dr Jahnecke said. “It's not something that I think in most biotech start-ups people are thinking about, but awareness is the first step. There's no Alzheimer’s equivalent in the animal health world; it's not going to work everywhere. At this year's Bio International Convention in the US, we had for the first time three of the largest animal health companies - Zoetis, Merck, and Boehringer Ingelheim - presenting, and their rooms were packed.”
“It's basically a bidirectional approach, where clinical findings from patients are used to design early studies in animal models of spontaneously occurring diseases such as cancer or diabetes,” he explained. “Then, the information in those animal studies will later be used to predict the efficacy and safety of future therapeutics in clinical trials. Therefore, the idea is to de-risk the clinical programme in human health.”
Veeva Systems’ Animal Health segment: Serving uniqueness
Within R&D, rigorous regulatory standards for regulating animal medicines mean managing thousands of documents, across multiple regions. At Veeva Systems, Animal Health - very much a customer segment – equips companies for navigating that management journey.
“The animal health industry is highly consolidated, much more so than human pharma,” Dr Jahnecke explained. “For example, the top four companies hold about half of the entire market. We're working with large animal health manufacturers, but we are also working closely with companies of any size, even very small animal health companies.”
“When it comes to commercial cloud, we have nine global animal health customers,” he continued. “Here, we're really focusing on two areas:, customer engagement with our CRM Suite and also the other area, content and digital asset management with Vault PromoMats. We have three of the top four animal health customers using our multi-channel CRM Suite, and the top four animal health companies using Vault PromoMats.”
Of course, just like humans, animals come in myriad species-dictated shapes and sizes.
“What is unique, I think, first and foremost, [is that] species are unique,” he said. “The fact that our customers deal with a number of different species has very direct implications on our data model and our software. They require, also, unique engagement models and marketing capabilities. What we can offer is species- and product-specific detailing. We can differentiate between species while referencing the same product, which is very typical in animal health. You have this, for example, in antiphlogistics, registered to use in dogs and in cats. That helps us to deliver immediate value for any new animal health customers.”
“Another set of very important features that we have is order management,” he went on. “It's not as relevant in human pharma. In fact, arguably it's not at all. It is important for consumer health, for animal health, where sales reps actually take orders […] Then - very, very important - is account management, especially in the more consolidated business units in animal health, such as poultry and swine.”
“One day we can talk to an animal health company that just wants to modernise their regulatory departments and processes, and then we can talk to another company that comes to us and wants to transition to a unified platform,” Dr Jahnecke explained. “That can include all three areas: clinical, regulatory, and quality. At the same time, they want to reimagine their business processes. Those could be really transformational strategic initiatives versus more incremental approaches to modernise and move away from manual processes that are still very prevalent in animal health. In essence, they're looking for a solution that helps them make this transition. Our most advanced for this area, regulatory phase, application is clearly Vault RIM.”
Rigorous standards and in-animal testing
“I think it is a typical misconception that animal health is less rigorous and complex compared to human health,” Dr Jahnecke posited. “What most human drug developers do not understand are the key advantages we have in animal health clinical development, which is the de-risking of candidates and time to market or animal health products.”
Indeed, there is no phase one or two in animal health clinical development: all of the early-stage work is done in the actual target animal.
“We test in dogs for a new dog medicine,” Dr Jahnecke explained. “Then, we go into the clinic where we test there as soon as we have basic safety information available. That is a massive difference [to human health studies].”
“I think the constraints that come in, or maybe perhaps regulatory differences - they are then somewhat similar,” he continued. “Animal health is very rigorous and complex. The drugs are highly regulated, and the regulatory landscape is super complex, but [humans] have additional needs.”
About the interviewee
Dr Stefan Jahnecke is passionate about animals and worked as a practicing veterinarian prior to joining Pfizer in 2000. While there, he held strategy and marketing roles in the company's animal health division, that later became Zoetis with the IPO in 2013. He led global marketing for new products and its US cattle business. Just prior to joining Veeva in 2021, Dr Jahnecke was self-employed as a management consultant for animal health strategy and commercial development. Born in Bonn, Germany, he earned a doctorate in veterinary medicine from Justus Liebig University in Giessen. Dr Jahnecke currently resides in the United States.